FDA Grants Fast Track Designation to Soquelitinib for Relapsed/Refractory PTCL

The FDA has granted fast track designation to soquelitinib (CPI-818) for the treatment of adult patients with relapsed or refractory peripheral T-cell lymphoma (PTCL) after at least 2 lines of systemic therapy.¹

“The granting of fast track designation by the FDA highlights the significant unmet need for patients with relapsed or refractory PTCL,” Richard A. Miller, MD, co-founder, president and chief executive officer of Corvus Pharmaceuticals, stated in a news release.¹ “The current treatment options for these patients provide limited efficacy and are associated with significant toxicity, and there are no FDA–fully approved agents. There continues to be strong interest in soquelitinib from investigators at sites with deep experience treating T-cell lymphomas, and we are on track to initiate patient enrollment in our registrational phase 3 trial in PTCL in the third quarter 2024.”

The FDA previously granted orphan drug designation to the agent for the treatment of patients with T-cell lymphoma.² The investigational, oral small molecule was designed to selectively inhibit ITK, an enzyme that is mostly expressed in T cells and involved in T-cell and natural killer cell immune function.¹

Previously the agent demonstrated antitumor activity in patients with advanced, refractory T-cell lymphomas in a phase 1/1b trial (NCT03952078). Findings from the study served as the basis for the company’s ongoing registrational phase 3 in patients with relapsed PTCL.¹

In September 2023, the company confirmed that it had completed an end-of-phase/pre-phase 3 meeting with the FDA regarding their plans to launch the phase 3 trial, which is designed to enroll 150 patients with relapsed PTCL following no more than 3 prior lines of therapy. Eligible patients will be randomly assigned 1:1 to 200 mg of soquelitinib twice daily or standard chemotherapy. The primary end point of the trial will be progression-free survival. Secondary end points will include objective response rate and overall survival.³

Updated data from the phase 1 trial were presented at the 2023 International Conference on Malignant Lymphoma with a data cutoff of May 18, 2023.4 Of the 30 patients who were enrolled in the trial and treated at the optimum 200-mg twice daily dose, the median age was 60 years (range, 29-81). Most patients were male (43.3%) and had received a median of 3 prior lines of therapy (range, 1-18). The most prevalent histology was PTCL not otherwise specified (n = 13).⁵

Among the 20 patients evaluable for tumor response there were 3 complete responses (CR) and 3 partial responses (PR). One patient with a CR and 2 with a PR remained on therapy. A total of 10 patients remained on therapy, including 6 who had not undergone their first response assessment. For patients with an absolute lymphocyte count (ALC) above 900/mm3, objective responses were seen in 6 of 14 patients with disease control occurring in 12 patients. No objective responses were seen in the 6 patients with an ALC below 900/mm³.⁴

Additionally, investigators collected serial blood and tumor samples in a responding patient. Single-cell RNA sequencing from paired samples comparing baseline and on-treatment specimens illustrated an increase in tumor-infiltrating CD8-positive T cells; an increase in cytolytic effector molecules such as granzymes and perforin in the T cells; and an increase in T-effector memory cells, which can mediate malignant cell death.⁴

In addition, flow cytometry analysis of paired blood samples from baseline and on treatment suggested a similar pattern in both CD8- and CD4-positive T cells. Additional findings indicated that treatment with soquelitinib reversed T-cell–expressing exhaustion markers, which is a known mechanism of resistance to checkpoint inhibition.⁴

Regarding safety, the most common adverse effects (AEs) that occurred in at least 10% of patients included anemia, diarrhea, nausea, pyrexia, COVID-19, upper respiratory tract infection, bilirubin increase, neutrophil count decrease, platelet count decrease, white blood cell count decrease, hypokalemia, pruritus, and rash. The most frequent grade 3 or greater AE that occurred in at least 2 patients was decreased neutrophil count.⁵

References

1. Corvus Pharmaceuticals granted FDA fast track designation for soquelitinib for treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). News release. Corvus Pharmaceuticals. August 1, 2024. Accessed August 1, 2024. http://investor.corvuspharma.com/news-releases/news-release-details/corvus-pharmaceuticals-granted-fda-fast-track-designation
2. Corvus Pharmaceuticals announces orphan drug designation granted to soquelitinib for the treatment of T cell lymphoma. News release. Corvus Pharmaceuticals. February 8, 2024. Accessed August 1, 2024. http://investor.corvuspharma.com/news-releases/news-release-details/corvus-pharmaceuticals-announces-orphan-drug-designation-granted
3. Corvus Pharmaceuticals confirms planned initiation of soquelitinib (CPI-818) phase 3 registrational clinical trial in peripheral T cell lymphoma following meeting with FDA. News release. Corvus Pharmaceuticals, Inc. September 6, 2023. Accessed August 1, 2024. https://corvuspharma.gcs-web.com/news-releases/news-release-details/corvus-pharmaceuticals-confirms-planned-initiation-soquelitinib
4. Corvus Pharmaceuticals presents new CPI-818 interim data at the International Conference on Malignant Lymphoma. News release. Corvus Pharmaceuticals. June 15, 2023. Accessed August 1, 2024. http://investor.corvuspharma.com/news-releases/news-release-details/corvus-pharmaceuticals-presents-new-cpi-818-interim-data
5. Ding N, Xie Y, Reneau J, et al. Itk inhibitor induces Th1 skewing and host anti-tumor response mediated by CD8+ TEMRA cells in refractory T cell lymphoma patients. Hematol Oncol. 2023;41(suppl 2):13-17. doi:10.1002/hon.3164_193